Efficacy and safety of tisagenlecleucel in Japanese adult patients with relapsed/refractory diffuse large B-cell lymphoma.

BACKGROUND: Tisagenlecleucel demonstrated a high rate of durable response in adult patients with relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) in the pivotal global phase 2 JULIET study. Here, we report the efficacy and safety of tisagenlecleucel in the Japanese subgroup. METHODS: JULIET (NCT02445248) is a single-arm, open-label, multicenter, phase 2 study involving adult patients with r/r DLBCL who either relapsed after or were ineligible for autologous stem cell transplant. Primary endpoint was best overall response rate (ORR; complete response [CR] + partial response [PR]) as judged by an independent review committee. RESULTS: In Japan, of 17 patients enrolled, 9 were infused with tisagenlecleucel and completed ≥ 3 months of follow-up. Best ORR was 77.8% (7/9; 95% confidence interval, 40.0-97.2), with 5 patients (55.6%) in CR and 2 (22.2%) in PR. Cytokine release syndrome (CRS) occurred in 6 patients (66.7%), with grade 3 CRS in 2 patients (Penn grading scale). Two patients received tocilizumab. Two deaths (22.2%) occurred more than 30 days after tisagenlecleucel infusion due to disease progression, neither of which were related to tisagenlecleucel. CONCLUSION: Tisagenlecleucel showed a high best ORR with a manageable safety profile, thus offering a new treatment option in selected Japanese patients with r/r DLBCL.

[A Case of Early Detection of Hepatocellular Carcinoma using Abdominal Ultrasonography after Endoscopic Submucosal Dissection for Early Gastric Cancer].

We treated an 82-year-old man with early gastric cancer using endoscopic submucosal resection.Ultrasonography, which was performed to screen for metastasis, revealed hepatocellular carcinoma, and the tumor was curatively resected.Ultrasonography can be considered a useful examination tool to detect double cancer, even in cases of early cancer.

[A Case of Primary Squamous Cell Carcinoma of the Jejunum in the Ultra-Elderly].

We treated a 91-year-old man with squamous cell carcinoma that originated from his jejunum, which is very rare; only 8 cases have been reported previously.Surgery was performed because of the small bowel obstruction caused by the large cancerous mass, but he died 23 days later.Early detection and early treatment are important, especially for the ultra-elderly from a standpoint of tolerating surgery.

Cost Effectiveness Analysis of Tisagenlecleucel for the Treatment of Adult Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma in Japan.

There are limited treatment options and substantial unmet needs for adult patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) in Japan. In 2019, tisagenlecleucel, a CD19-directed chimeric antigen receptor T cell therapy, was approved for r/r DLBCL in Japan. The efficacy and safety of tisagenlecleucel were demonstrated in the pivotal phase II single-arm JULIET trial. The objective of the current study was to assess the cost-effectiveness of tisagenlecleucel treatment strategy versus current standard of care (salvage chemotherapy treatment strategy) for the treatment of patients with r/r DLBCL in Japan. A three-state partitioned survival model was constructed from a Japanese public healthcare payer's perspective, with the following three health states: progression-free survival, progressive/relapsed disease, and death. Because the tisagenlecleucel arm included patients who did or did not receive the infusion, a decision-tree structure was used to partition patients based on their infusion status. Treatment efficacy and costs were based on tisagenlecleucel-infused patients for those who received the infusion; for non-infused patients, they were based on standard salvage chemotherapy. The efficacy inputs for tisagenlecleucel-infused patients and salvage chemotherapy were based on observed data in the JULIET trial and the international SCHOLAR-1 meta-analysis, respectively, before year 3. Afterward, all patients were assumed to have no further progression and to incur the mortality risk of long-term DLBCL survivors. The base case analysis explored a lifetime horizon (44 years), with costs and effectiveness discounted 2.0% annually, and it used a monthly model cycle. Direct costs were considered in the base case, composed of pretreatment costs, treatment costs, adverse events management costs, follow-up costs before progression, subsequent SCT costs, post-progression costs, and terminal care costs. Total incremental costs, life years (LYs), and quality-adjusted life years (QALYs) were compared for tisagenlecleucel versus salvage chemotherapy. The incremental cost-effectiveness ratio (ICER) was estimated as the costs per QALY gained, and a threshold of ¥7.5 million was used to assess whether tisagenlecleucel is cost effective. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel and salvage chemotherapy were 7.24 and 4.35 years, respectively; the corresponding QALYs were 5.42 and 2.57 years, respectively. The discounted incremental LYs and QALYs comparing tisagenlecleucel to salvage chemotherapy were estimated as 2.89 and 2.85 years, respectively. Over a lifetime horizon, the model estimated that tisagenlecleucel had a total incremental cost of ¥15,590,335 (discounted) versus salvage chemotherapy. Tisagenlecleucel was associated with an ICER of ¥5,476,496 per QALY gained compared to salvage chemotherapy. Extensive sensitivity analyses supported the base-case findings. Tisagenlecleucel is a cost-effective treatment strategy for r/r DLBCL compared to salvage chemotherapy treatment strategy from a Japanese public healthcare payer's perspective.

Ofatumumab combined with chlorambucil for previously untreated chronic lymphocytic leukemia: a phase I/II, open-label study in Japan.

Elderly/comorbid patients with chronic lymphocytic leukemia (CLL) require low-toxicity treatments. Internationally, the standard treatment for such patients is chlorambucil and an anti-CD20 therapy; however, chlorambucil is not approved in Japan. The aim of the present study was to evaluate the safety, efficacy and pharmacokinetics of ofatumumab in combination with chlorambucil in Japanese patients with previously untreated CLL who were inappropriate for fludarabine-based therapy. Ten patients were enrolled and treated in this study, all of whom received at least one dose of the study drugs. The tolerability of the treatment was confirmed initially with three patients. The overall response rate was 50%, as determined by the Independent Review Committee (IRC) with computerized tomography. All patients were alive at follow-up, and only one patient had progressive disease. The most common treatment-related adverse events (AEs) were thrombocytopenia (n = 10), neutropenia (n = 9) and rash (n = 6). One grade 3 serious AE related to the study drug occurred (hypoxia). The results indicate that ofatumumab combined with chlorambucil is an effective treatment for Japanese CLL patients, with a manageable safety profile.